FXL12_HUMAN
ID FXL12_HUMAN Reviewed; 326 AA.
AC Q9NXK8; B3KSJ8; Q9H5K4;
DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=F-box/LRR-repeat protein 12;
DE AltName: Full=F-box and leucine-rich repeat protein 12;
DE AltName: Full=F-box protein FBL12;
GN Name=FBXL12; Synonyms=FBL12;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Colon mucosa, and Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [5]
RP FUNCTION.
RX PubMed=23707388; DOI=10.1016/j.cellsig.2013.05.012;
RA Mallampalli R.K., Kaercher L., Snavely C., Pulijala R., Chen B.B., Coon T.,
RA Zhao J., Agassandian M.;
RT "Fbxl12 triggers G1 arrest by mediating degradation of calmodulin kinase
RT I.";
RL Cell. Signal. 25:2047-2059(2013).
RN [6]
RP VARIANT HIS-63.
RX PubMed=21248752; DOI=10.1038/nature09639;
RA Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H.,
RA Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J.,
RA Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M.,
RA Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L.,
RA Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J.,
RA Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A.,
RA Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K.,
RA Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.;
RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene
RT PBRM1 in renal carcinoma.";
RL Nature 469:539-542(2011).
CC -!- FUNCTION: Substrate-recognition component of the SCF (SKP1-CUL1-F-box
CC protein)-type E3 ubiquitin ligase complex. Mediates the
CC polyubiquitination and proteasomal degradation of CAMK1 leading to
CC disruption of cyclin D1/CDK4 complex assembly which results in G1 cell
CC cycle arrest in lung epithelia. {ECO:0000269|PubMed:23707388}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with SKP1 and CUL1. {ECO:0000250}.
CC -!- INTERACTION:
CC Q9NXK8; P49918: CDKN1C; NbExp=6; IntAct=EBI-719790, EBI-519256;
CC Q9NXK8; Q8NF50-2: DOCK8; NbExp=3; IntAct=EBI-719790, EBI-10174653;
CC Q9NXK8; P57678: GEMIN4; NbExp=3; IntAct=EBI-719790, EBI-356700;
CC Q9NXK8; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-719790, EBI-739832;
CC Q9NXK8; Q9H0A6: RNF32; NbExp=2; IntAct=EBI-719790, EBI-724829;
CC Q9NXK8; P63208: SKP1; NbExp=7; IntAct=EBI-719790, EBI-307486;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NXK8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NXK8-2; Sequence=VSP_008859;
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK000195; BAA91002.1; -; mRNA.
DR EMBL; AK027004; BAB15622.1; -; mRNA.
DR EMBL; AK093760; BAG52760.1; -; mRNA.
DR EMBL; CH471106; EAW84051.1; -; Genomic_DNA.
DR EMBL; BC001586; AAH01586.1; -; mRNA.
DR CCDS; CCDS12218.1; -. [Q9NXK8-1]
DR CCDS; CCDS82287.1; -. [Q9NXK8-2]
DR RefSeq; NP_001303865.1; NM_001316936.1.
DR RefSeq; NP_001303866.1; NM_001316937.1. [Q9NXK8-2]
DR RefSeq; NP_001303867.1; NM_001316938.1. [Q9NXK8-2]
DR RefSeq; NP_001303868.1; NM_001316939.1. [Q9NXK8-2]
DR RefSeq; NP_001303869.1; NM_001316940.1. [Q9NXK8-2]
DR RefSeq; NP_001303870.1; NM_001316941.1. [Q9NXK8-2]
DR RefSeq; NP_001303871.1; NM_001316942.1. [Q9NXK8-2]
DR RefSeq; NP_060173.1; NM_017703.2. [Q9NXK8-1]
DR AlphaFoldDB; Q9NXK8; -.
DR SMR; Q9NXK8; -.
DR BioGRID; 120200; 97.
DR IntAct; Q9NXK8; 19.
DR MINT; Q9NXK8; -.
DR STRING; 9606.ENSP00000247977; -.
DR iPTMnet; Q9NXK8; -.
DR PhosphoSitePlus; Q9NXK8; -.
DR BioMuta; FBXL12; -.
DR DMDM; 38257780; -.
DR EPD; Q9NXK8; -.
DR jPOST; Q9NXK8; -.
DR MassIVE; Q9NXK8; -.
DR MaxQB; Q9NXK8; -.
DR PaxDb; Q9NXK8; -.
DR PeptideAtlas; Q9NXK8; -.
DR PRIDE; Q9NXK8; -.
DR ProteomicsDB; 83107; -. [Q9NXK8-1]
DR ProteomicsDB; 83108; -. [Q9NXK8-2]
DR Antibodypedia; 25087; 155 antibodies from 27 providers.
DR DNASU; 54850; -.
DR Ensembl; ENST00000247977.9; ENSP00000247977.3; ENSG00000127452.9. [Q9NXK8-1]
DR Ensembl; ENST00000585379.5; ENSP00000467359.1; ENSG00000127452.9. [Q9NXK8-2]
DR Ensembl; ENST00000591009.1; ENSP00000468369.1; ENSG00000127452.9. [Q9NXK8-2]
DR GeneID; 54850; -.
DR KEGG; hsa:54850; -.
DR MANE-Select; ENST00000247977.9; ENSP00000247977.3; NM_017703.3; NP_060173.1.
DR UCSC; uc002mme.3; human. [Q9NXK8-1]
DR CTD; 54850; -.
DR GeneCards; FBXL12; -.
DR HGNC; HGNC:13611; FBXL12.
DR HPA; ENSG00000127452; Low tissue specificity.
DR MIM; 609079; gene.
DR neXtProt; NX_Q9NXK8; -.
DR OpenTargets; ENSG00000127452; -.
DR PharmGKB; PA134934043; -.
DR VEuPathDB; HostDB:ENSG00000127452; -.
DR eggNOG; KOG1947; Eukaryota.
DR GeneTree; ENSGT00390000003354; -.
DR HOGENOM; CLU_024577_1_0_1; -.
DR InParanoid; Q9NXK8; -.
DR OMA; SCLAMPK; -.
DR OrthoDB; 1046098at2759; -.
DR PhylomeDB; Q9NXK8; -.
DR TreeFam; TF313434; -.
DR PathwayCommons; Q9NXK8; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9NXK8; -.
DR SIGNOR; Q9NXK8; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 54850; 38 hits in 1122 CRISPR screens.
DR ChiTaRS; FBXL12; human.
DR GenomeRNAi; 54850; -.
DR Pharos; Q9NXK8; Tdark.
DR PRO; PR:Q9NXK8; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9NXK8; protein.
DR Bgee; ENSG00000127452; Expressed in thymus and 195 other tissues.
DR ExpressionAtlas; Q9NXK8; baseline and differential.
DR Genevisible; Q9NXK8; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IBA:GO_Central.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0051726; P:regulation of cell cycle; IBA:GO_Central.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR032675; LRR_dom_sf.
DR Pfam; PF12937; F-box-like; 1.
DR SMART; SM00256; FBOX; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS50181; FBOX; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Leucine-rich repeat; Reference proteome; Repeat;
KW Ubl conjugation pathway.
FT CHAIN 1..326
FT /note="F-box/LRR-repeat protein 12"
FT /id="PRO_0000119857"
FT DOMAIN 1..47
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT REPEAT 51..78
FT /note="LRR 1"
FT REPEAT 86..111
FT /note="LRR 2"
FT REPEAT 113..133
FT /note="LRR 3"
FT REPEAT 161..185
FT /note="LRR 4"
FT REPEAT 186..211
FT /note="LRR 5"
FT REPEAT 212..236
FT /note="LRR 6"
FT REPEAT 237..261
FT /note="LRR 7"
FT REPEAT 266..291
FT /note="LRR 8"
FT VAR_SEQ 1..53
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_008859"
FT VARIANT 63
FT /note="L -> H (found in a renal cell carcinoma case;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21248752"
FT /id="VAR_064712"
SQ SEQUENCE 326 AA; 37026 MW; 1BC5C2A40CB91D68 CRC64;
MATLVELPDS VLLEIFSYLP VRDRIRISRV CHRWKRLVDD RWLWRHVDLT LYTMRPKVMW
HLLRRYMASR LHSLRMGGYL FSGSQAPQLS PALLRALGQK CPNLKRLCLH VADLSMVPIT
SLPSTLRTLE LHSCEISMAW LHKQQDPTVL PLLECIVLDR VPAFRDEHLQ GLTRFRALRS
LVLGGTYRVT ETGLDAGLQE LSYLQRLEVL GCTLSADSTL LAISRHLRDV RKIRLTVRGL
SAPGLAVLEG MPALESLCLQ GPLVTPEMPS PTEILSSCLT MPKLRVLELQ GLGWEGQEAE
KILCKGLPHC MVIVRACPKE SMDWWM
